A total of 927 MMR gene mutation carriers (360 MLH1, 442 MSH2, 85 MSH6 and 40 PMS2) from 315 families enrolled in the Colon Cancer Family Registry, were genotyped for the single nucleotide polymorphisms (SNPs): rs16892766 (8q23.3), rs6983267 (8q24.21), rs719725 (9p24), rs10795668 (10p14), rs3802842 (11q23.1), rs4444235 (14q22.2), rs4779584 (15q13.3), rs9929218 (16q22.1), rs4939827 (18q21.1), rs10411210 (19q13.1) and rs961253 (20p12.3).
Rectal tumors were significantly associated with rs4939827 (OR = 4.85, P = 0.002) and rs6983267 (OR = 3.00, P = 0.036), suggesting that carriers of risk alleles at these loci had increased susceptibility to development of rectal cancer rather than colon cancer.
The odds ratios between SMAD7 and colon cancer among individuals reporting recent aspirin/nonsteroidal anti-inflammatory drug use was 0.60 (95% CI, 0.43-0.85) for the CC genotype of the rs4939827 polymorphism and 1.69 (95% CI, 1.20-2.38) for the TT genotype of the rs1295371 polymorphism.